The International Registry of Werner Syndrome has existed at the University of Washington for the past 15 years to: 1. ascertain and genotype additional pedigrees from around the world (The Registry is the sole organization in the U.S. that provides genetic confirmation of the WS); 2. establish and cryopreserve cell materials including Epstein-Barr virally transformed peripheral blood B lymphocytes cell lines (LCL), primary skin fibroblast cultures and immortalized skin fibroblast cultures from affected patients and other family members from these pedigrees; 3. provide fresh peripheral blood samples, cultured cell materials, WRN cDNA, anti-WRN antibodies to colleagues at the University of Washington and elsewhere; and 4. maintain and expand the University of Washington International Registry of Werner Syndrome Database on the participant information on a secure web server and a separate WorldWeb site with public information for clinicians and for a general audience seeking information regarding Werner syndrome. This proposal would continue these functions with the following enhancements: 1. the establishment of a selection reversible hTERT immortalized WS and control fibroblasts; 2. sequence analysis of candidate genes in Werner syndrome patients and atypical Werner syndrome cases with no apparent WRN or LMNA mutations; 3. as a part of the University of Washington Department of Pathology's newly developed networked computer system we proposed transfer of the Registry's local secure intranet function (clinical and laboratory data) and the public website to a new system with enhanced security, automated backup, and automated viral screens; and 5. to make a major effort to obtain large numbers of cryopreserved skin explants and other tissues from autopsied WS subjects to provide additional primary cultures and biochemical assayable materials for investigators here at the University of Washington and other institutes. [unreadable] [unreadable] [unreadable]